Method of reducing plant growth height using phenylalkylmorpholines

ABSTRACT

Novel phenylalkylcycloamines, their preparation, agents containing these compounds, and methods for regulating plant growth.

This application is a division of application Ser. No. 743,683, filed onJune 11, 1985, now abandoned.

German Laid-Open Application Nos. DOS 2,752,096, DOS 2,656,747, DOS2,720,612, DOS 2,753,278 and DOS 2,830,127 and European Patent No. 5,541disclose that phenylpropylamines possess fungicidal activity. Thesecompounds have only an insignificant effect on plant growth.

We have found that extending the propylene radical connecting the tworing structures, which therefore leads to substances of the formula I##STR1## where the radicals R¹ are identical or different substituentsand are each selected from the group consisting of lower alkyl,cycloalkyl, alkoxy, lower acyl and halogen, R² and R³ are each hydrogenor C₁ -C₃ -alkyl, z is straight-chain C₄ -C₁₀ -alkylene which isunsubstituted or substituted by not more than three C₁ -C₄ -alkylradicals, X is oxygen, sulfur or (CH₂)_(p), m is 0 to 3 and p is 0 to 2,gives compounds which have little or no fungicidal activity but insteadsurprisingly exhibit interesting growth-regulating actions.

R¹ is, for example, CH₃, C₂ H₅, n-propyl, isopropyl, n-butyl, isobutyl,tert.-butyl, tert.-amyl, 1,1-dimethylbutyl, 1,1-dimethylpentyl,cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, methoxy, ethoxy,propoxy, tert.-butoxy, acetyl, propionyl, benzoyl, pivaloyl, F, Cl, Bror I.

R² and R³ independently of one another are each hydrogen, methyl, ethyl,propyl or isopropyl.

z is, for example, (CH₂)₄, CH₂ CHCH₃ CH₂ CH₂, (CH₂)₅, CH₂ CH₂ CHCH₃ CH₂CH₂, (CH₂)₃ CHCH₃ CH₂, CH₂ CHCH₃ CH₂ CHCH₃ CH₂, (CH₂)₆, (CH₂)₄ CHCH₃CH₂, (CH₂)₇, (CH₂)₅ CHCH₃ CH₂, (CH₂)₈, (CH₂)₉ or (CH₂)₁₀.

Examples of amino radicals of the formula I are those derived frompyrrolidine, piperidine, 3-methylpiperidine, 3,5-dimethylpiperidine,morpholine, 2,6-cis-dimethylmorpholine, 2,6-transdimethylmorpholine,2,6-dimethylthiamorpholine and hexamethyleneimine.

The novel compounds can be used as active ingredients in growthregulators.

For the purposes of the present invention, important intermediatecompounds for the preparation of phenylalkylamines are phenylalkylhalides of the formula II ##STR2## which in turn can be prepared by, forexample, condensation reactions or other reactions to form C-C bonds, asshown in equation 1.

EQUATION 1 ##STR3##

Reactions of this type to form C-C bonds are described in, for example,Angew. Chem. 86 (1974), 50.

A possible, convenient variation of the aromatic substitution of thephenylalkyl halides comprises reacting appropriate known halides of theformula II (where (R¹)_(m) may also be hydrogen) ##STR4## in whichhalogen is preferably chlorine but may furthermore be bromine or iodine,some of these halides being available commercially.

The preparation process described below can be carried out using thesehalides.

EQUATION 2 ##STR5##

The synthesis of appropriate phenylpropyl halides, which are describedin European Patent No. 9,077, can also be extrapolated withoutdifficulty to phenylalkyl chlorides possessing a longer chain.

Reaction of the corresponding phenylalkyl halides (II) ##STR6## with thesecondary cyclic amines (IV) ##STR7## gives the phenylalkylaminesaccording to the invention.

The reaction of (II) with (IV) takes place spontaneously in the presenceor absence of a solvent, at in general from 50° to 200° C., preferablyfrom 130° to 170° C. Suitable solvents are tetrahydrofuran, toluene,xylene, dimethylformamide and dimethylacetamide. It is sometimesadvantageous to add a neutralizing agent, such as Na₂ CO₃, K₂ CO₃ orNaHCO₃, to the reaction mixture.

PREPARATION EXAMPLES FOR INTERMEDIATES

A. 2,4-Dimethyl-4-phenylbutyl chloride

(a) 192 g of propionaldehyde are added dropwise to a solution of 402 gof 2-phenylpropan-1-al and 12 g of sodium hydroxide in 1 l of methanolin the course of 6 hours. Stirring is continued for one hour, afterwhich the mixture is neutralized with glacial acetic acid (pH=6),stirred overnight and evaporated down, the residue is taken up with CH₂Cl₂ /H₂ O, and the solution is extracted with CH₂ Cl₂. The organic phaseis washed with water, dried over Na₂ SO₄, evaporated down again anddistilled to give 178 g of 2,4-dimethyl-4-phenylbut-2-en-1-al of boilingpoint 108°-120° C./0.5 mbar.

(b) The aldehyde obtained (178 g of 2,4-dimethyl-4-phenylbut-2-en-1-al)is hydrogenated in 600 ml of methanol with 40 g of Raney nickel at from60° to 70° C. and under a hydrogen pressure of 100 bar. The catalyst isfiltered off, the filtrate is evaporated down and the residue isdistilled to give 137 g of 2,4-dimethyl-4-phenylbutan-1-ol. Thereactions are repeated in order to produce a larger stock.

(c) 219 g of 2,4-dimethyl-4-phenyl-butan-1-ol are added dropwise to 161g of thionyl chloride, the mixture is stirred overnight at roomtemperature and then for 2 hours at 140° C., and the crude product isdistilled to give 150 g of 2,4-dimethyl-4-phenylbutyl chloride ofboiling point 84°-86° C./0.1 mm.

B. 2-Methyl-5-phenylpentyl chloride

0.26 mole of 3-bromo-2-methylpropyl chloride in 50 ml of tetrahydrofuranis added dropwise to a suspension of 0.45 mole of phenylethylmagnesiumchloride in 500 ml of tetrahydrofuran at -15° C. 13 ml of a 0.5 molarsolution of Li₂ CuCl₄ in tetrahydrofuran are then added dropwise at -15°C.

The mixture is heated to room temperature and 360 ml of saturated NH₄ Clsolution are added, after which the mixture is extracted with ether, thesolution is dried over Na₂ SO₄ and evaporated down, and the residue isdistilled to give 30 g of 2-methyl-5-phenylpentyl chloride of boilingpoint 83°-87° C./0.1 mbar (the procedure is repeated).

C. 5-p-tert.-Butylphenyl-2-methylpentyl chloride

27 g of tert.-butyl chloride are added dropwise to an ice-cooled mixtureof 52 g of 2-methyl-5-phenylpentyl chloride and 4.9 g of FeCl₃. Themixture is stirred for 7 hours at 50° C. and for 12 hours at roomtemperature, and taken up in methylene chloride, the solution is washedwith water, dried over Na₂ SO₄ and evaporated down, and the residue isdistilled to give 40 g of 5-p-tert.-butylphenyl-2-methylphenyl chlorideof boiling point 114°-118° C./0.2 mbar.

The phenylalkyl chlorides of the formula (II) which are summarized inthe Table below can be prepared from known intermediates in accordancewith the Examples above.

                  TABLE 1                                                         ______________________________________                                         ##STR8##                                                                     Com-                                                                          pound                                                                         No.(R.sup.1).sub.m                                                            z-          ybp. °C./mbar                                              ______________________________________                                         1H         (CH.sub.2).sub.4                                                                              Br 76° 0,4                                  24-tBu     (CH.sub.2).sub.4                                                                              Cl                                                 34-Br      (CH.sub.2).sub.4                                                                              Cl                                                 4H         CHCH.sub.3 CH.sub.2 CHCH.sub.3 CH.sub.2                                                       Cl84-6° 0.1                                 54-acetyl  (CH.sub.2).sub.4                                                                              Br                                                 64-OCH.sub.3                                                                             (CH.sub.2).sub.5                                                                              Cl                                                 7H         (CH.sub.2).sub.5                                                                              Br 78-80° 0.2                               84-t-Bu    (CH.sub.2).sub.5                                                                              Cl112-115° 0.4                              94-Cl      (CH.sub.2).sub.5                                                                              Cl106-112° 0.2                             104-CH.sub.3                                                                              (CH.sub.2).sub.5                                                                              Cl116-122° 0.8                             11H         (CH.sub.2).sub.2 CHCH.sub.3 (CH.sub.2).sub.2                                                  Cl80-82° 0.2                               12H         (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                          Cl83-87° 0.2                               134-t-Bu    (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                          Cl120-2° 0.2                               14 2-CH.sub.3                                                                             (CH.sub.2).sub.5                                                                              Cl90-91° 0.2                               154-cyclohexyl                                                                            (CH.sub.2).sub.5                                                                              Br                                                164-propionyl                                                                             (CH.sub.2).sub.5                                                                              Cl                                                17H         (CH.sub.2).sub.6                                                                              Cl86-90° 0.3                               18H         (CH.sub.2).sub.4 CHCH.sub.3 CH.sub.2                                                          Cl116-120° 0.2                             194-Br      (CH.sub.2).sub.6                                                                              Cl                                                204-OCH.sub.3                                                                             (CH.sub.2).sub.6                                                                              Cl                                                214-OtBu    (CH.sub.2).sub.6                                                                              Cl                                                224-cyclohexyl                                                                            (CH.sub.2).sub.6                                                                              Cl                                                234-tBu     (CH.sub.2).sub.4 CHCH.sub.3 CH.sub.2                                                          Cl130° 0.1 mm                              244-tBu     (CH.sub.2).sub.6                                                                              Cl120-2° 0.2 mm                            254-tBu     CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                          Cl                                                264-CH.sub.3                                                                              CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                          Cl                                                274-t-amyl  CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                          Cl                                                282,4-Cl.sub.2                                                                            CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                          Cl                                                292,3,4-Cl.sub.3                                                                          CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                          Cl                                                30H         (CH.sub.2).sub.7                                                                              Cl116-122° 0.1                             314-tBu     (CH.sub.2).sub.7                                                                              Cl                                                32H         (CH.sub.2).sub.10                                                                             Cl                                                ______________________________________                                    

If the method below is appropriately modified, the phenylalkyl halidesof the formula (II) can be converted to the phenylalkylamines of theformula (I).

PREPARATION EXAMPLE FOR A COMPOUND ACCORDING TO THE INVENTIONN-(2-Methyl-5-phenylpentyl)-2,6-cis-dimethylmorpholine

20 g of 2-methyl-5-phenylpentyl chloride and 35 g of2,6-cis-dimethylmorpholine are heated at 150° C. for 10 hours, afterwhich the mixture is left to cool, taken up with CH₂ Cl₂, washed withwater, dilute NaOH and once again with water, dried over Na₂ SO₄ andevaporated down, and the residue is distilled to give 18 g of a productof boiling point 130°-132° C./0.4 mbar.

The phenylalkyl halides, for example those shown in Table 1, can beconverted to novel phenylalkylamine of the formula I (Table 2) by asimilar method; those compounds which are characterized by physical datahave been prepared, and their biological action investigated. Thecompounds which are not characterized are expected, on the basis ofstructural similarity, to have a similar action.

                                      TABLE 2                                     __________________________________________________________________________     ##STR9##                                                                     Com-                                                                          pound                                                                         No. (R.sup.1).sub.m                                                           z-  X    R.sup.2      R.sup.3                                                                          bp. °C./mbar                                  __________________________________________________________________________    101 H    (CH.sub.2).sub.4                                                                           CH.sub.2                                                                         H  H  116-120°/0.3                            102 4-tBu                                                                              (CH.sub.2).sub.4                                                                           O  CH.sub.3                                                                         CH.sub.3                                          103 4-Br (CH.sub.2).sub.4                                                                           O  CH.sub.3                                                                         CH.sub.3                                          104 H    (CH.sub.2).sub.5                                                                           O  CH.sub.3                                                                         CH.sub.3                                                                         134-6°/0.1 m                            105 H    (CH.sub.2).sub.5                                                                           CH.sub.2                                                                         H  CH.sub.3                                          106 4-OCH.sub.3                                                                        (CH.sub.2).sub.5                                                                           CH.sub.2                                                                         H  H                                                 107 H    (CH.sub.2).sub.5                                                                           O  C.sub.2 H.sub.5                                                                  C.sub.2 H.sub.5                                   108 H    (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                       O  CH.sub.3                                                                         CH.sub.3                                                                         130-2°/0.4                              109 4-Cl (CH.sub.2).sub.5                                                                           -- H  H                                                 110 4-tBu                                                                              (CH.sub. 2).sub.5                                                                          O  CH.sub.3                                                                         CH.sub.3                                                                         165-8°/0.3                              111 4-tBu                                                                              (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                       O  CH.sub.3                                                                         CH.sub.3                                                                         149-153/0.2                                    112 4-tBu                                                                              (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                       S  CH.sub.3                                                                         CH.sub.3                                          113 4-tBu                                                                              (CH.sub.2).sub.3 CHCH.sub.3 CH.sub.2                                                       CH.sub.2                                                                         CH.sub.3                                                                         CH.sub.3                                          114 4-tBu                                                                               ##STR10##   O  CH.sub.3                                                                         CH.sub.3                                          115 4-tBu                                                                               ##STR11##   CH.sub.2                                                                         CH.sub.3                                                                         CH.sub.3                                                                         166-172°/0.1                            116 4-CH.sub.3                                                                         (CH.sub.2).sub.5                                                                           O  CH.sub.3                                                                         CH.sub.3                                                                         140-2°/0.3                              117 4-cyclo-                                                                           (CH.sub.2).sub.5                                                                           O  CH.sub.3                                                                         CH.sub.3                                              hexyl                                                                     118 4-acetyl                                                                           (CH.sub.2).sub.4                                                                           O  CH.sub.3                                                                         CH.sub.3                                          119 H    (CH.sub.2).sub.6                                                                           O  CH.sub.3                                                                         CH.sub.3                                                                         128-130°/0.1                            120 H    (CH.sub.2).sub.6                                                                           CH.sub.2                                                                         H  CH.sub.3                                          121 H    (CH.sub.2).sub.4 CHCH.sub.3 CH.sub.2                                                       O  CH.sub.3                                                                         CH.sub.3                                                                         135-8°/0.2                              122 4-OtBu                                                                             (CH.sub.2).sub.6                                                                           O  CH.sub. 3                                                                        CH.sub.3                                          123 4-cyclo-                                                                           (CH.sub.2).sub.6                                                                           O  CH.sub.3                                                                         CH.sub.3                                              hexyl                                                                     124 4-tBu                                                                              (CH.sub.2).sub.6                                                                           O  CH.sub.3                                                                         CH.sub.3                                                                         162-5°/0.2                              125 4-tBu                                                                              (CH.sub.2).sub.6                                                                           O  H  H                                                 126 4-tBu                                                                              (CH.sub.2).sub.6                                                                           CH.sub.2                                                                         H  H                                                 127 4-tBu                                                                              (CH.sub.2).sub.4 CHCH.sub.3 CH.sub.2                                                       O  CH.sub.3                                                                         CH.sub.3                                                                         159-160°/0.2                            128 4-tBu                                                                              (CH.sub.2).sub.4 CHCH.sub.3 CH.sub.2                                                       CH.sub.2                                                                         H  H                                                 129 4-tBu                                                                              CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                       O  CH.sub.3                                                                         CH.sub.3                                          130 4-t-amyl                                                                           CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                       O  CH.sub.3                                                                         CH.sub.3                                          131 2,4-Cl.sub.2                                                                       CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                       O  CH.sub.3                                                                         CH.sub.3                                          132 2,3,4-Cl.sub.3                                                                     CH.sub.2 CHCH.sub.3 (CH.sub.2).sub.4                                                       O  CH.sub.3                                                                         CH.sub.3                                          133 H    (CH.sub.2).sub.7                                                                           O  CH.sub.3                                                                         CH.sub.3                                                                         148-152°/0.2                            134 4-tBu                                                                              (CH.sub.2).sub.7                                                                           CH.sub.2                                                                         H  H                                                 135 4-tBu                                                                              (CH.sub.2).sub.7                                                                           O  CH.sub.3                                                                         CH.sub.3                                          136 H    (CH.sub.2).sub.10                                                                          O  CH.sub.3                                                                         CH.sub.3                                          137 4-tBu                                                                              (CH.sub.2).sub.2 CHCH.sub.3 (CH.sub.2).sub. 2                                              O  CH.sub.3                                                                         CH.sub.3                                                                         145-150/0.1                                    138 H    (CH.sub.2).sub.3 CHC.sub.2 H.sub.5 CH.sub.2                                                O  CH.sub.3                                                                         CH.sub.3                                                                         160-162/0.7                                    139 H    CHCH.sub.3 CH.sub.2 CHC.sub.2 H.sub.5 CH.sub.2                                             O  CH.sub.3                                                                         CH.sub.3                                                                         128-133/0.5                                    140 H    CHCH.sub.3 CH.sub.2 CHCH.sub.3 CH.sub.2                                                    O  CH.sub.3                                                                         CH.sub.3                                                                         134-138/0.7                                    141 H    (CH.sub.2).sub.2 (CHCH.sub.3).sub.2 CH.sub.2                                               O  CH.sub.3                                                                         CH.sub.3                                                                         140-142/0.7                                    __________________________________________________________________________

For example, the growth-regulating action of the novel phenylalkylaminescan be determined in the manner described below.

1. Rice seedling test

The test procedure is described by W. Rademacher and J. Jung in Z.Acker- und Pflanzenbau 150 (1981), 363-371. This test is used tocharacterize growth-regulating activity. The compounds 110, 111 and 124showed a substantially superior shortening action compared with thestandard compounds chlormequat chloride and fenpropimorph.

Concentrations of active ingredient (mole/l) which result in 50%shortening of the second leaf sheath in rice seedlings (Girona variety)

    ______________________________________                                        Active ingredient                                                                              Concentration                                                ______________________________________                                        chlormequat chloride                                                                           1.5 × 10.sup.-2                                        fenpropimorph    1.0 × 10.sup.-4                                        compound 110     1.4 × 10.sup.-5                                        compound 111     3.5 × 10.sup.-5                                        compound 116     1.9 × 10.sup.-5                                        compound 124     2.7 × 10.sup.-5                                        ______________________________________                                    

2. Sunflowers--postemergence method

Sunflowers of the Spanners Allzweck variety were grown on culturesubstrates provided with sufficient nutrients, in plastic vessels havinga diameter of about 12.5 cm. The novel compounds to be tested, in theform of an aqueous formulation, were sprayed onto the plants afteremergence. The growth-regulating action observed was confirmed at theend of the experiment by measuring the height of growth. The measuredvalues thus obtained were expressed as a ratio of the height of growthof the untreated plants.

For treatment with, for example, 6 mg of active ingredient per vessel,the amines 110, 111, 121, 127 and 137 showed a superior shorteningaction compared with the standard compounds cycocel and fenpropimorph.

    ______________________________________                                                         Height of shoot                                              Active ingredient                                                                              (% of control)                                               ______________________________________                                        chlormequat chloride                                                                           87.5                                                         fenpropimorph    81.0                                                         compound 110     74.5                                                         compound 111     71.3                                                         compound 121     71.3                                                         compound 127     76.1                                                         compound 137     70.7                                                         control          100                                                          ______________________________________                                    

3. Seed treatment in the case of wheat, barley and corn

Treatment of the seed of wheat (Kolibri variety), barley (Arimirvariety) and corn (Inrakorn variety) with 1 g of active ingredient perkg of seed resulted in a pronounced reduction in the height of growth.In this respect, compound No. 111, in particular, proved superior to thestandard compounds chlormequat chloride and fenpropimorph.

    ______________________________________                                        (Data as a percentage of the particular control)                              Active ingredient                                                                            Wheat       Barley  Corn                                       ______________________________________                                        chlormequat chloride                                                                         87          96      100                                        fenpropimorph  92          91      101                                        compound 111   24          57       63                                        ______________________________________                                    

We claim:
 1. A method of reducing the growth height in plants, whichcomprises allowing an effective amount of phenylalkylamine of theformula ##STR12## where the radical R¹ is selected from the groupconsisting of lower alkyl, R² and R³ are C₁ -C₃ -alkyl, z is astraight-chain C₄ -C₁₀ -alkylene which is unsubstituted or substitutedby not more than three C₁ -C₄ -alkyl radicals, X is oxygen, and m is 1,to act on plants or on their propagation stock.